chr2-191031990-C-T

Position:

• chr2-191031990-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003151.4(STAT4):​c.2045-474G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,168 control chromosomes in the GnomAD database, including 2,494 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2494 hom., cov: 32)
• Consequence: STAT4 NM_003151.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.162

Genes affected

STAT4 (HGNC:11365): (signal transducer and activator of transcription 4) The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is essential for mediating responses to IL12 in lymphocytes, and regulating the differentiation of T helper cells. Mutations in this gene may be associated with systemic lupus erythematosus and rheumatoid arthritis. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Aug 2011]

STAT4-AS1 (HGNC:55764): (STAT4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAT4	NM_003151.4	c.2045-474G>A		intron_variant		ENST00000392320.7	NP_003142.1
STAT4-AS1	NR_136318.1	n.244-182C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAT4	ENST00000392320.7	c.2045-474G>A		intron_variant		1	NM_003151.4	ENSP00000376134	P1
STAT4-AS1	ENST00000456176.5	n.244-182C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25586 AN: 152050 Hom.: 2494 Cov.: 32

Gnomad AFR AF: 0.0913

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.168 AC: 25585 AN: 152168 Hom.: 2494 Cov.: 32 AF XY: 0.171 AC XY: 12751 AN XY: 74390

Gnomad4 AFR AF: 0.0912

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.186

Alfa AF: 0.186 Hom.: 3751

Bravo AF: 0.163

Asia WGS AF: 0.237 AC: 823 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3024896; hg19: chr2-191896716;